Objective: This study examines the prevalence of drug and poly-drug use and their associated factors among female sex workers (FSW) in Iran. Methods: We analyzed data from a bio-behavioral surveillance survey of 1,347 FSW across 13 major cities in Iran in 2015. Two outcome measures were defined: i) past-month "any drug use", a binary variable defined as none or any; and ii) a three-category past-month "poly-drug use" variable defined as none, only one drug, and more than one drug. Correlates of these two study outcomes were assessed using multivariable logistic regression and multinomial logistic regression, respectively. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported. Results: We found that 24.9% (95% CI: 16.1, 36.4) and 13.5% (95% CI: 8.1, 21.5) of FSW reported past-month any drug use and poly-drug use, respectively. Longer sex work career (AOR 2.44 [95% CI: 1.28, 4.63]), unstable housing (AOR 2.56 [1.17, 5.64]), past-year experience of sexual violence (AOR 1.61 [1.15, 2.27]), and incarceration (AOR 2.02 [1.23, 3.32]) were positively associated with any drug use. Similarly, FSW who were unstably housed (AOR 3.4